10.22037/ijpr.2021.114754.15020
December 2020
April 2021
Type of article: Review
The genus Ferulago: A review on ethnopharmacology, phytochemistry, and pharmacology
Yahya Rahimpour1,2, Abbas Delazar3, Solmaz Asnaashari4 and Parina Asgharian3,5*
1
Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.
2
Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
3
Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
4
Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
5
Department of Pharmacognosy, School of Pharmacy, Tabriz University of Medical Sciences,
Tabriz, Iran.
Running title: The genus Ferulago, a review
*Corresponding author:
Parina Asgharian, Drug Applied Research Center and School of Pharmacy, Tabriz University of
Medical Sciences, Tabriz 51664, Iran, Tel: +98 (914)1771694; Fax: +98 (413) 33347581.
E-mail: parina.asgharian@gmail.com
Abstract
The Ferulago genus appertains to the Umbelliferae family comprises of 49 species which are
mainly distributed in Asia, Europe, and Africa. This paper aims to review the morphological
properties of Ferulago species, herbal components, and their pharmacological properties.
The information of this review paper has been collected from journals available in databases
including Science Direct, Web of Science, Scopus, PubMed, EBSCO, Google Scholar, and
Hindawi up to March 2020. In traditional medicine, the genus of Ferulago has been used to treat
intestinal worms, snake bites, wound skin infections, diseases of the spleen and gastrointestinal
tract, and headache. It not only has been used traditionally as a preservative agent to dairy, oil
ghee, and meat but also giving them a pleasant taste. The main components of Ferulago spp. are
monoterpenes, sesquiterpenes, coumarin, furanocoumarin, flavonoids, and terpenoids have been
the reason for antimicrobial, antioxidant, anticoagulant, antidiabetic, Alzheimer, and larvicidal
properties of this plant.
This review confirms that many traditional uses of some Ferulago species have now been
validated by modern pharmacology research. Rigorous investigations of all the species
of Ferulago concerning phytochemical and pharmacological properties, mainly their mechanism
of action, efficacy, and safety might offer a context for researchers to prosper plant-derived
medications like anti-diabetes, antibiotics, and sedatives treating drugs, and the key to directing
clinical trials.
Keywords: Ferulago, Essential oil, Pharmacological activity, Herbal medicine, Phytotherapy.
Introduction
Herbal used in traditional and modern medicine presents a valuable source of secondary
metabolites and different pharmacological and biological activities. Hence, they could be utilized
as a lead compound to produce new drugs and treat numerous diseases (1). The Apiaceae or
Umbelliferae, commonly known as the parsley, carrot, or celery family, is one of the biggest
plant families in the world usually characterized with aromatic plants with hollow stems (2).
Several plants belonging to this family are well-known as vegetables, culinary, and medicinal
plants, including Apium gravolence, Foeniculum vulgare, Centella asiatica, Pimpinella anisum,
Cuminum cyminum, Carum carvi, Ligusticum officinale, Coriandrum sativum, Anethum
graveolens , Ammi visnaga, Anthriscus cerefolium, Ferulago angulata, and Ferula assa-foetida
(3). Plants of the Apiaceae family are commonly aromatic and pungent owing to the existence of
essential oil or oleoresin in their diverse organs (4). Among several Umbelliferae families, the
species belonging to the genus Ferulago W. Koch. are broadly employed in traditional medicine.
The genus Ferulago W. Koch. (called Chavil or Chavir in Persian, Çakşır or Çağşır in Turkey)
appertains to the Umbelliferae family consisting of 49 species which are mostly distributed in
Asia, Europe, and Africa(5, 6).The occurrence of several bioactive secondary metabolites,
including coumarin, coumarin esters, furanocoumarin, flavonoids, quinones, steroids, essential
oils, steroids, and terpenoids are owing to their pharmacological activities (7). Extensive studies
have been conducted to evaluate the ethnomedicinal uses of Ferulago species antibacterial,
antioxidant, Alzheimer, anti-diabetics, anti-malaria, anti-coagulant, and aphrodisiac effects. The
information of this review paper has been collected from journals available in databases
including Science Direct, Web of Science, Scopus, PubMed, EBSCO, Google Scholar, and
Hindawi up to March 2020. The keywords and search terms contained “Ferulago”, “Ferulago
spp.” “essential oil of Ferulago”, “phytochemistry and Ferulago”, “coumarins and Ferulago”,
“bioactive compounds and Ferulago”, “pharmacological activity and Ferulago”. Therefore, we
conducted the present review article to provide a complete overview of a current state of
knowledge on botany, ethnomedicinal uses, phytochemistry, and the most noticeable
pharmacological effects of species belonging to the genus Ferulago.
The botany of Ferulago plants
The Ferulago genus appertains to the Umbelliferae family and comprises 49 species which are
mainly distributed in Asia, Europe, and Africa (8). The genus Ferulago is distributed in Turkey
with 34 species, out of which 18 are endemic (9). The 8 species exist in Iran, out of which three
are endemic (10). According to the plantlist website, the genus Ferulago consists of 48 accepted
species name and 13 unassessed species(11). Table 1 depicts name of accepted species and their
synonyms. Ferulago genus is 60-150 cm tall; annual or perennial plants grow at altitudes of
1900- 3200m above the sea level with yellow fruits. They are characterized with persistent bracts
and bracteoles and small flowers which are widely distributed in Turkey, Iraq, and west of Iran
(from the flora of Iran, particularly in Kermanshah, Ilam, Lorestan, and Kurdistan)(8, 12, 13).
Pictures of Ferulago bernardii and fruits of ferulago stellata are shown in Fig.1. The high
distribution of Ferulago spp. in these areas suggests that the core center of the biodiversity of
genus Ferulago is Anatolia. Based on taxonomy the species of this genus resemble Prangos and
Ferula species. They are widely used in the Anatolia region for several purposes (7, 14). The
most studied species is F. angulata which is divided based on ovaries, the flowering of in
fluorescence, and fibers (rather absence or presence of trichomes) into two subspecies: F.
angulate subsp. angulata and F. angulate subsp. Carduchorum by Chamberlain in 1987(15).
No.
1
2
3
4
Ferulago species
F. angulata (Schltdl.) Boiss.
F. angulata subsp. carduchorum
(Boiss. & Hausskn.) D. F. Chamb
F. antiochia Saya & Miski
F. armena (DC.) Bernardi
5
F. aucheri Boiss.
6
7
8
F. asparagifolia Boiss.
F. bernardii Tomk. & Pimenov
F. biumbellata Pomel
9
10
11
12
13
14
15
16
F. blancheana Post ex Boiss.
F. bracteata Boiss. & Hausskn
F. brachyloba Boiss. & Reut.
F. cassia Boiss.
F. contracta Boiss. & Hausskn
F. daghestanica Schischk.
F. fieldiana Rech.f.
F. galbanifera (Mill.) W. D. J. Koch
17
18
19
20
F. glareosa Kandemir & Hedge
F. granatensis Boiss.
F. idaea Özhatay & Akalin
F. humulis Boiss.
Synonyms
F. angulata Schltdl., F. linearifolia Boiss., F. trifida Boiss.
F. carduchorum Boiss. & Hausskn., F. abbreviata C. C. Towns.,
F. pauciradiata Boiss. & Heldr., Ferula armena DC.,
F. bourgaei Boiss. Ferula gandogeri M.Hiroe. Ferula kochii M.Hiroe.
F. sintenisii Gand.
Ferula taurica (Schlschk.) M. Hiroe, F. galbanifera var. brachyloba
Boiss., F. taurica Schischk.
F. longistylis Boiss.
Ferula sulcata var. biumbellata (Pomel),
Ferula lutea var. mouretii (Maire) Maire. Batt.
Ferula sulcata var. mouretii Maire
Ferula brachyloba (Boiss. & Reut.) Nyman
F. amani Post ex Boiss.
Ferula fieldiana (Rech.f.) M. Hiroe
Ferula daghestanica (Schischk.) M. Hiroe, Ferula campestris Besser,
Ferula meoides L., Ferula galbaniifera Mill, F. campestris (Besser)
Grecescu, F. meoides (L.) Boiss. F. dodonaei Kostel,
Ferula granatensis (Boiss.) Steud.
F. pumila Boiss.
21
22
23
F. isaurica Peşmen
F. kurdica Post
F. lutea (Poir.) Grande
24
F. macrocarpa (Fenzl) Boiss.
25
26
27
28
F. macedonica Micevski & E.
Mayer
F. macrosciadea Boiss. & Balansa
F. mughlae Peşmen
F. nodosa (L.) Boiss.
29
F. pachyloba (Fenzl) Boiss.
30
31
32
33
34
35
36
37
F. phialocarpa Rech. f. & Riedl
F. sandrasica Peşmen & Quezel
F. platycarpa Boiss. & Balansa
F. sartorii Boiss.
F. scabra Pomel
F. serpentinica Rech.f.
F. setifolia K. Koch
F. stellata Boiss.
38
39
F. silaifolia (Boiss.) Boiss.
F. subvelutina Rech. f
40
F. sylvatica (Besser) Rchb.
41
F. sylvatica subsp. confusa (Velen.)
Hartvig
Elaeoselinum mangenotianum Emb., Ferula capillaris Link ex
Spreng., Ferula capillifolia Link., Ferula lutea (Poir.) Maire,
Ferula lutea var. microcarpa (Maire)Maire, Ferula pomelii M.Hiroe,
Ferula sulcata Desf., Ferula sulcata var. crassicosta (Pomel) Batt.,
Ferula sulcata var. leptocarpa (Pomel) Batt.,
Ferula sulcata var. microcarpa Maire,
Ferula sulcata var. parvifolia (Pomel) Batt. F. barrelieri Guss.,
F. capillaris (Link ex Spreng.) Cout., F. capillifolia (Link) Franco,
F. communis Petter ex Nyman, F. crassicosta Pomel,
F. leptocarpa Pomel F. nodiflora Koch, F. parvifolia Pomel,
F. sulcata (Desf.) Ledeb., Ligusticum luteum Poir.
Ferula lophoptera (Boiss.) Benth. & Hook. f., Ferula mesopotamica, F.
lophoptera Boiss.
Ferula cretica (Spreng.) M. Hiroe, Ferula geniculata Guss., Ferula
nodosa (L.) Benth. & Hook. f., Ferula rigida Ten., Peucedanum
nodosum L, F. geniculata Boiss.
Ferula cappadocica (Bornm.) M. Hiroe, Ferula pachyloba Fenzl,, F.
cappadocica Bornm.
F. asperula Freyn & Sint
Ferula algiersia M.Hiroe, Ferula sulcata var. scabra (Pomel) Batt.
Ferula pauciflora K. Koch, Ferula setifolia K. Koch, Ferula sylvatica
Szov. ex Boiss., F. oxyptera Boiss., F. pauciflora K. Koch
Ferula silaifolia (Boiss) M. Hiroe
Ferula subvelutina (Rech. f.) M. Hiroe, Ferula turcomanica
(Schischk.)M. Hiroe, F. turcomanica Schischk
Ferula barrelieri Ten., Ferula commutata (Racher) M. Hiroe, Ferula
ferulago var. commutata Rochel, Ferula microphylla M.Bieb. ex
Schur, Ferula monticola (Boiss. & Heldr.) Neilr.,
Ferula myriophylla M.Bieb. ex Besser, Ferula schischkinii M.Hiroe,
Ferula sylvatica Besser, Ferula verticillata Maerkl.
F. athamantifolia Schur, F. commutata (Rochel) Degen, F.
latiloba Schischk., F. monticola Boiss. & Heldr., F. orphanidis Boiss.
& Heldr., F. rocheliana Nyman, F. transsilvanica Schur
F. confuse Velen.
42
43
44
45
46
47
48
F. syriaca Boiss
F. ternatifolia Solanas, M.B.Crespo
& García-Martín
F. thirkeana Boiss
F. trachycarpa Boiss.
F. thyrsifolia (Sm.) Koch
F. trojana Akalın & Pi
F. vesceritensis Coss. & Durieu ex
Batt.
F. cypria H.Wolff
Ferula insularis (H. Wolff) M. Hiroe, F. frigida Boiss., F. insularis H.
Wolff
Ferula thyrsifolia Sm.
Table 1. Accepted genus of Ferulago species based on The Plant List.
Fig1. a) The Ferulago bernardii in the flowering stage, b) the fruits of the Ferulago stellata.
Traditional use of Ferulago spp.
Ferulago like Ferula and Prangos species have been traditionally utilized back in history in folk
medicine for the medicament of hemorrhoids, and intestinal worms, peptic, sedative,
carminative, digestive, aphrodisiac, snakebite, wound skin infections, headache, diseases of the
gastrointestinal tract and spleen (5, 16). Due to the aromatic property of Ferulago, some of them
have been applied in Iranian tradition as spices in different foods, such as dairy and meat
products, for increasing the flavor and as an aroma. They have also been employed as natural
preservatives for enhancing food expiration date (8, 16, 17). Bakhtiari nomads use F. angulata to
make some foods and Nomads of Fars province utilize this plant to flavor yogurt. The F.
angulata also used as a sedative, food-digestive, tonic, antibacterial, and antiparasitic(18). In
Turkish traditional medicine, the aerial parts of a few members of this genus are used as an
immunostimulant, tonic, sedative, digestive, anti-bronchitis, flavor, vermicidal, anthelmintic, and
anti-peptic (19, 20). Likewise, the root parts are used for the treatment of dermatological
disorders and cancers and as an aphrodisiac and are preferred as fodder to improve animal
productivity (7). The seeds are applied for eye pains in the form of inhalation (8). It has been
reported that dried or fresh leaves of Ferulago are used as foot deodorant by indigenous people
of the north of Iraq (21).
Phytochemistry of essential oils from the genus Ferulago species
Essential oils or volatile oils are the phytochemical complexes of different aromatic components,
mainly monoterpenoids and sesquiterpenoids, which are obtained from plant materials, for
instance leaves, fruits, seeds buds, flowers, roots, and bark. They are characterized with having
strong odor generally lower density than water, being volatile, rarely colored, liquid, lipophilic,
and soluble in organic solvents (7). In spite of the way that these volatile oils involve around 20–
60 constituents, just a few of them exist at high amounts (20–70%) in correlation with different
constituents existing in low sums (22). These phytochemicals assume a vital part in the
protection of the herbs from herbivores, insects, bacteria, fungi, viruses, and also help to attract
pollinators (23). These essential oils could be extracted with conventional methods (steam
distillation, hydrodistillation (HD), organic solvent extraction) and innovative techniques (In situ
microwave-generated hydrodistillation, supercritical carbon dioxide, microwave steam diffusion,
microwave hydrodiffusion and gravity, and microwave steam distillation). Among these
methods, the hydro-distillation method is the most prevalent technique for obtaining essential
oils (7, 24, 25). The method of extraction, drying methods, genotypic variation, geographical
origin of the plant, stage of the development, and part of the plant used may drastically affect the
composition of essential oils of plants (26-28). Based on the literature, researches have revealed
that the species of Ferulago genus are appropriate for the extraction of essential oils and many of
them have been evaluated for chemical compositions, composition including F. macedonica, F.
angulata, F. carduchorum, F. phialocarpa, F. contracta, F. macrocarpa, F. blancheana, F.
bernardii, F. pachyloba, F. longistylis, F. isaurica, F. syriaca, F. platycarpa, F. thyrsiflora, F.
sylvatica, F. nodosa, F. pauciradiata, F. asparagifolia, F. aucheri, F. galbanifera, F. confusa, F.
humilis, F. campestris, F. idaea, F. macrosciadia, F. mughlae, F. sandrasica, F. silaifolia, F.
trachycarpa, F. thirkeana, F. setifolia, F. subvelutina, F. stellata, F. capillaries F. trifida. Table
2 represents the main compounds of these essential oils, part of the herb that was used, methods
of extraction, percentage yield, class of components, and their references.
Plant
name
F.
macedonic
a
F. angulata
Yield
(%)
-
Metho
ds
HD
Part
0.66
Infloresce
nce
Aerial
parts
Aerial
parts
Flowers
0.54
Stems
0.43
Leaves
2.8
2.65
6.5
HD
HD
MAH
D
Fruits
F.carducho
rum
0.63
HD
3.2
Fruits
1.3
HD
F.
phialocarp
a
0.14
HD
F.contracta
0.68
F.
macrocarp
a
Leaves
0.89
HD
Aerial
parts
Aerial
parts
Infloresce
nce
Aerial
parts
1.3
Flowers
0.54
Leaves
0.4
Stems
-
HD
Flowers
Leaves
Main components (%)
Class
Re
f.
(29
)
α-Pinene (43.1), Sabinene (26.7)
Monoterpene (69.8)
α-Pinene (22.8), Sabinene (15.5)
Monoterpene (38.3)
α-Pinene (15.4), cis-Ocimene (30)
Monoterpene (45.5)
β-Phellandrene (16.5), αPhellandrene (27), p-Cymene
(10), α-Pinene (12)
β-Phellandrene (16), αPhellandrene (18), p-Cymene
(17.7), α-Pinene (21)
α-Pinene (16.8), α-Phellandrene
(20.7), p-Cymene (14.5), βPhellandrene (16)
Limonene (38), α-Pinene (18.1)
Limonene (35), α-Pinene (14)
Monoterpene (65.5)
Monoterpene (56.1)
Monoterpene (49)
(32
)
β-Phellandrene (32), αPhellandrene (13.8)
α-Pinene (26), cis-Ocimene
(24.5), Bornyl acetate (6.2)
Monoterpene (45.8)
(33
)
(18
)
cis-Ocimene (64-76), α-Pinene
(7.3-15)
(z)-β-Ocimene (43.5), α-Pinene
(18.2)
α-Pinene (41), α-Phellandrene
(14.2), β-Phellandrene (9.5)
α-Pinene (43.38), cisChrysanthenyl acetate (6) 2,4,5Trimethyl benzaldehyde (17).
β-Phellandrene (15), (E)-βOcimene(10) α-Phellandrene
(14.5), β-eudesmol (11)
β-Phellandrene (25), αPhellandrene (25)
β-Eudesmol (24.5 ), Spathulenol
(16), Citronellol (12)
β-Phellandrene (15.5), αPhellandrene (11.5)
Bornyl acetate (37.1), Terpinolene
(10)
Bornyl acetate (37.91), o-Cymene
(7.83)
(30
)
(31
)
Monoterpene (72.7)
Monoterpene (68)
Monoterpene (50.5),
Oxygenated monoterpene
(6.2)
Monoterpene (71.3-91)
Monoterpene (61.7)
Monoterpene (64.7)
Monoterpene (43.38),
Oxygenated monoterpene
(6) Oxygenated
hydrocarbon (17)
Monoterpene (39.5),
Oxygenated sesquiterpene
(11)
Monoterpene (50)
(34
)
(35
)
(36
)
(37
)
Oxygenated sesquiterpene
(40.5), oxygenated
monoterpene (12)
Monoterpene (27)
Oxygenated monoterpene
(37.1), Monoterpene (10)
Oxygenated monoterpene
(37.91), Monoterpene
(7.83)
(38
)
0.030.04
0.80
F.
blancheana
-
HD,
MAH
D
HD
F.
pachyloba
F.
longistylis
(39
)
(40
)
Bornyl acetate (49), 2,3,6Trimethyl benzaldehyde (7)
Oxygenated monoterpene
(49), Oxygenated
hydrocarbon (7)
Monoterpene (40.7)
Oxygenated monoterpene
(11.7), Sesquiterpene (10)
Oxygenated hydrocarbon
(20.3), Oxygenated
sesquiterpene (17.8)
Oxygenated hydrocarbon
(21), Monoterpene (17)
Monoterpene (49.2),
Oxygenated monoterpene
(11.6)
Monoterpene (35.5)
(41
)
Sabinene (23.2), Myrcene (17.5)
Bornyl acetate (11.7), βCaryophyllene (10.2)
E)-2-Decenal (20.3),
Caryophyllene oxide (17.8)
0.2
HD
-
HD
Aerial
parts
Aerial
parts
2,4,5-Trimethylbenzaldehyde
(21), α-Pinene (17)
α-Pinene (35), Bornyl
acetate(11.6), z-β-Ocimene (14.2)
1.5
HD
0.16
HD
Aerial
parts
Aerial
parts
(Z)-β-Ocimene (25.7), α-Pinene
(9.8)
2,3,6-trimethylbenzaldehyde
(32.7), Bornyl acetate (12.6)
Fruits
2,3,6-Trimethylbenzaldehyde
(29),(Z)-β-Ocimene (16), αPinene (17)
α-Pinene (31.5), Limonene (24.2),
Myrcene (17.0)
Terpinolene (42.1), Myrcene (27)
Nonacosane (25.5), Hexadecanoic
acid (14.8)
Myrcene (15.3), terpinolene
(12.5), 4,6-Guaiadiene (10.7)
Bornyl acetate (69.4), Terpinolene
(12.5)
12
HD
Fruits
HD
Roots
Aerial
parts
Fruits
0.7
0.08
F. syriaca
Oxygenated monoterpene
(62.9)
Oxygenated monoterpene
Flowers
Aerial
parts
Roots
6.4
F. isaurica
Fruit
Bornyl acetate (45.7), Borneol
(17.2)
Borneol and Bornyl acetate
HD
-
F.
bernardii
Aerial
parts
Flower
4.8
1.1
Roots
F.
platycarpa
0.07
HD
Aerial
parts
F.
thyrsiflora
F. sylvatica
0.80
HD
0.10
HD
Aerial
parts
Aerial
parts
Roots
-
2,3,6-Trimethylbenzaldehyde
(29.8), cis-Chrysanthenyl acetate
(24.2)
Spathulenol (31)
Sparhulenol (13)
2,3,6-Trimethylbenzaldehyde
(92.7)
Oxygenated hydrocarbon
(32.7), Oxygenated
monoterpene (12.6)
Oxygenated hydrocarbon
(29), Monoterpene (33)
Monoterpene (72.7)
Monoterpene (69.1)
Hydrocarbon (25.5), Fatty
acid (14.8)
Monoterpene (27.8),
Sesquiterpene (10.7)
Oxygenated monoterpene
(69.4), Monoterpene
(12.5)
Oxygenated hydrocarbon
(29.8), Oxygenated
monoterpene (24.2)
Oxygenated sesquiterpene
(31)
Oxygenated sesquiterpene
(13)
Oxygenated hydrocarbon
(92.7)
(42
)
(10
)
(16
)
(43
)
(43
)
(7)
(44
)
(43
)
(44
)
(43
)
(45
)
(45
)
(46
)
-
F. nodosa
F.
pauciradiat
a
Aerial
parts
Infloresce
nce
Fruits
Germacrene D (32.5)
Sesquiterpene (32.5)
Myrcene (29.2)
Monoterpene (29.2)
p-Cymene (45.8), 2,5 dimethoxy
p-Cymene (40)
α-Pinene (31)
Monoterpene (85.8)
Oxygenated hydrocarbon
(42.2), Monoterpene
(22.5)
Monoterpene (72.5)
-
M.D
3
HD
-
SDE
2,3,4-Trimethylbenzaldehyde
(42.2), α-Pinene(22.5)
-
SFE
Fruits
α-Pinene (55.5), Myrcene (10),
cis-β-Ocimene (7)
trans-Chrysanthenyl acetate (25),
2,3,6-Trimethyl benzaldehyde
(20.7), α-Pinene (23.7)
Fruits
Bornyl acetate (30.5), α-Pinene
(7), Germacrene D (8)
-
Roots
-
2,5, dimethoxy-p-Cymene (70), pCymene (12.5)
2,5, dimethoxy-p-Cymene (33),
Nonacosane (9), α-Pinene (9)
2,3, 6-trimethylbenzaldehyde (42),
α-Pinene (11)
2, 3, 6-trimethylbenzaldehyde
(38.9), Myrcene (18.2)
-
-
HD
Aerial
parts
-
M.D
Aerial
parts
Fruits
-
HD
Fruits
F. aucheri
-
MD
Fruits
α-Pinene (36)
F. confuse
-
MD
Fruits
F.
galbanifera
-
MD
Fruits
1.3
HD
Fruits
MD
Fruits
3.9
HD
Fruits
0.11
HD
Aerial
parts
Flowers
Roots
p-Cymene (24), 2,5-dimethoxy-pCymene (63.5)
trans-Chrysanthenyl acetate
(17.2), Limonene (10), p-Cymene
(12), α-Phellandrene (11),
α-Pinene (31.8), Sabinene (15.8),
Limonene (7)
Limonene (31), (Z)-b-Ocimene
(32)
Limonene (17.5), (Z)-β-Ocimene
(32.5), α-Pinene (12)
2,4,5-trimethyl benzaldehyde,
2,4,6-trimethyl benzaldehyde
F.asparagif
olia
F. humilis
F.
campestris
0.13
0.05
Monoterpene (31)
Oxygenated monoterpene
(25), Oxygenated
hydrocarbon (20.7)
Monoterpene (23.7)
Oxygenated monoterpene
(30.5), Monoterpene (7),
Sesquiterpene (8)
Monoterpene (82.5)
Monoterpene (42),
Hydrocarbon (9)
Oxygenated hydrocarbon
(42), Monoterpene (11)
Oxygenated hydrocarbon
(38.9), Monoterpene
(18.2)
Monoterpene (36)
Monoterpene (87.5)
Oxygenated monoterpene
(17.2), Monoterpene (33)
Monoterpene (54.6)
Monoterpene (63)
Monoterpene (62)
Oxygenated hydrocarbon
(47
)
(45
)
(48
)
(20
)
(49
)
(47
)
(50
)
(47
)
(47
)
(47
)
(51
)
(47
)
(51
)
(52
)
1.50
0.11
MAH
D
0.13
0.10
1.05
HD
6.4
Fruits
Aerial
parts
Flowers
Roots
Fruits
Roots
Fruits
α-Pinene (58.3–75)
Myrcene (36), α-Pinene (23), γTerpinene (10)
Myrcene (33.4–39.7), α-Pinene
(23)
p-Cymene (18.5), α-Pinene (16),
Carvacrol methyl ether (13),
2,3,6-Trimethyl benzaldehyde
(14)
p-Cymene (19.5), Carvacrol
methyl ether (78)
α-Pinene (25.4), Cubenol (12.7)
-
WD
Fruits
F. idaea
-
MD
Fruits
F.macrosci
adia
F. mughlae
-
MD
Fruits
-
MD
Fruits
-
HD
α-Pinene (45.5), Camphene (10.5)
-
Aerial
parts
Roots
-
Fruits
α-Pinene (53), Myrcene (3.9), βPhellandrene (11), Limonene (6)
α-Pinene (40.8), Germacrene D
(8)
α-Pinene (26.5), Camphene (5),
Caryophyllene oxide (6)
F.
sandrasica
-
MD
Fruits
-
HD
Herb
-
Roots
0.62
Leaves
0.02
HD
F. silaifolia
-
MD
Aerial
parts
Fruits
F.
trachycarp
a
-
MD
Fruits
-
HD
Fruits
7.3
Fruits
α-Pinene (37.5), Borneol (9.5)
α-Pinene (28), δ-3-Carene (14.2),
Limonene (26)
Ocimene (30.5), α-Pinene (17.8),
δ-3-Carene (27.4)
Limonene (29), Terpinolene (14),
α-Pinene (15.6)
α-Pinene (5.5), TransChrysanthenyl acetate (83.5)
γ-Terpinene (27.8)
(Z)-β- Ocimene (34.1), α-Pinene
(8)
(Z)-p-Ocimene (30.7), Myrcene
(27.7)
Monoterpene (58.3–75)
Monoterpene (69)
(23
)
Monoterpene (56.4-62.7)
(53
)
(47
)
Monoterpene (34.5),
Oxygenated monoterpene
(13), Oxygenated
hydrocarbon (14)
Oxygenated monoterpene
(78), Monoterpene (19.5)
Monoterpene (25.4),
Oxygenated sesquiterpene
(12.7)
Monoterpene (56)
(47
)
(47
)
(54
)
Monoterpene (37.5),
Oxygenated monoterpene
(9.5)
Monoterpene (72.9)
Monoterpene (40.8),
Sesquiterpene (8)
Monoterpene (31.5),
Oxygenated sesquiterpene
(6)
Monoterpene (68.2)
(47
)
(55
)
Monoterpene (75.7)
(56
)
(57
)
(47
)
(47
)
(51
)
(58
)
Monoterpene (58.6)
Oxygenated monoterpene
(83.5), Monoterpene (5.5)
Monoterpene (27.8)
Monoterpene (42.1)
Monoterpene (58.4)
4.1
HD
Fruits
Ferulagone (64), Germacrene D
(14), α-Pinene (10)
-
MD
Fruits
Ferulagone (56), Germacrene D
(12), α-Pinene (9)
F. setifolia
0.26
HD
Aerial
parts
F.
subvelutina
-
HD
Aerial
parts
Aerial
parts
Aerial
parts
Aerial
parts
Aerial
parts
2,4,5-Trimethyl benzaldehyde
(77.8), 2,3,4-Trimethyl
benzaldehyde (6.2)
Limonene (27), α-Phellandrene
(23.1), α-Pinene (13.3)
Limonene (30), Terpinolene (14),
α-Pinene (15.5),
2,4,5-Trimethyl benzaldehyde
(61.1)
α-Pinene (35.8), Limonene (30.9)
F.
thirkeana
F. stellata
F.capillaris
0.60
HD
-
HD
1.5
HD
Oxygenated monoterpene
(64), Sesquiterpene (14),
Monoterpene (10)
Oxygenated monoterpene
(56), Sesquiterpene (12),
Monoterpene (9)
Oxygenated hydrocarbon
(84)
(59
)
Monoterpene (63.4)
(60
)
(61
)
(60
)
(62
)
(63
)
Monoterpene (58.5)
Oxygenated hydrocarbon
(61.1)
Monoterpene (66.7)
Oxygenated monoterpene
(35.39), Sesquiterpene
(8.68)
1.4
Flowers
Monoterpene (53.8),
Oxygenated monoterpene
(9.5)
0.8
Roots
Suberosin (20.7), Cuparene (6), β- Coumarin (20.7),
Sesquiterpene (12.5)
Barbatene (6.5)
1.3
Stems
(E)-β-Ocimene (20.7), α-Pinene
Monoterpene (43.3),
(22.6), Bornyl acetate (8.5)
oxygenated monoterpene
(8.5)
1.6
Leaves
(E)-β-Ocimene (25.7), Bornyl
Monoterpene (45.3),
acetate (16.7), α-Pinene (19.6)
Oxygenated monoterpene
(16.7)
1.4
Fruits
(E)-β-Ocimene (30.5), Bornyl
Monoterpene (48.5),
acetate (11), α-Pinene (18)
Oxygenated monoterpene
(11)
HD: Hydrodistillation, SDE: Simultaneous Distillation Extraction, MAHD: Microwave-assisted
distillation.
F. trifida
Isobornyl acetate (25.73),
Verbenol (9.66), E-βCaryophyllene (8.68)
(E)-β-Ocimene (37.3), α-Pinene
(16.5), Bornyl acetate (9.5)
Table 2. Main constituents of the volatile oils of 35 Ferulago species studied before
According to data of the volatile oils extracted from various Ferulago spp., it is clear that
every species and each part of the plant have a diversified set of main compounds. Therefore, it
is hard to find similarity among the species of this genus concerning the chemicals. Several
compounds, like α-Pinene, p-Cymene 2,3,6-trimethyl benzaldehyde, cis-Chrysanthenyl acetate,
α-Phellandrene, Sabinene, (Z)-β-Ocimene, Limonene, Myrcene, Terpinolene, Nonacosane, and
δ-Cadinene, have been detected as main components of the volatile oils of many Ferulago
species. To date, analysis has shown that the α-Pinene is a major compound of several Ferulago
species; hence, this might be regarded as a perpetual constituent for the genus (7). There are
(28
)
(64
)
certain other notable points to report; primarily, the compound of spathulenol was the major
component from aerial parts of only two species namely, F. sylvatica and F. thyrsiflora (45).
Secondly, the compound of ferulagone was found as the main compound of only F. thirkeana
obtained from its fruits (59). Thirdly, carvacrol methyl ether obtained with MD from fruits of F.
macrosciadia and F. idaea was the major component of only these two species (47).
Furthermore, Cecchini et al. compared the composition of the volatile oil from roots and fruits of
F. campestris from two sites of collection and two periods of time. They found significant
differences in the percentages of (2,3,6) ‐trimethyl benzaldehyde (14.8–27.9% in the roots
gathered in the summer, 65.2% in roots gathered in the fall) and α-Pinene (58.3-75% in the roots
gathered in the summer, 19.3% in the roots gathered collected in the fall)(23).
Phytochemistry of plant extracts from the genus Ferulago species
Phytochemical investigations on Ferulago species have shown the presence of various secondary
metabolites including coumarins, coumarin esters, furanocoumarins, aromatic compounds,
monoterpenes, sesquiterpenes, flavonoids, quinones, and stilbene. Table 3 depicts the main
phytochemicals that have been isolated and characterized from Ferulago species. Up to now,
several researches have been done to distinguish active compounds from different parts of
ferulago genus, from which about 73 (three simple coumarins, sixteen furanocoumarins, five
dihydro-furanocoumarin, four sesquiterpene coumarin, twelve prenylated coumarins, six
pyranocoumarin, nine flavonoids, and eighteen miscellaneous compounds) bioactive compounds
were isolated. Based on literature, coumarins and their derivatives are the most prevalent
secondary metabolites on the Ferulago species and might be used as a chemotaxonomic marker
in the genus Ferulago (65). The classification of different types of coumarins and various
biological applications of each compound was reviewed by Venugopala et. al. (66).
Compounds
Umbelliferone
Class
Simple
coumarin
Structure
Plants and References
F. asparagifolia (67), F. cassia (8), F.
bernardii(68)
6-hydroxymethyl
herniarin
Simple
coumarin
F. trifida (69)
Crenulatin
Simple
coumarin
F. trachycarpa (14)
Imperatorin
Furanocouma
rin
F. trifida (69)
Isoimperatorin
Furanocouma
rin
F. trifida (69)
Isopimpinellin
Furanocouma
rin
F. carduchorum (70)
Isooxypeucedanin
Furanocouma
rin
F. turcomanica (71)
Oxypeucedanin
Furanocouma
rin
Oxypeucedanin
Hydrate (Prangol)
Furanocouma
rin
F. bernardii (68), F. meoides (72) F.
capillaries, F. brachyloba (65) F.
turcomanica (71), F. grandatensis (73),
F. subvelutina (74), F. platycarpa (75),
F. sylvatica (76), F. angulate (77), F.
trifida (69)
F. capillaries, F. brachyloba (65), F.
meoides (72), F. sylvatica (76), F.
turcomanica, F. subvelutina (74), F.
angulate (77), F. trifida (69)
Oxypeucedanin
methanolate
Furanocouma
rin
F. trifida (69)
Oxypeucedanin
hydrate senecioate
Furanocouma
rin
F. capillaris (65)
Psoralen
Furanocouma
rin
F. turcomanica (71), F. bernardii (68)
8-methylpsoralen
Furanocouma
rin
F. asparagifolia (67)
Xanthotoxin
Furanocouma
rin
F. syriaca (19) F. isaurica (19), F.
bracteata, F. pachyloba, F.
trachycarpa, F. blancheana (78), F.
angulate (77), F. carduchorum (70), F.
trifida (69)
8-(1,1
dimethylallyl)
bergaptol
Furanocouma
rin
F. syriaca (19), F. capillaris(65)
(-)-Pranferol
Furanocouma
rin
F. capillaris (65)
Bergamotin
Furanocouma
rin
F. capillaris (65)
Bergapten
Furanocouma
rin
Alatol
Furanocouma
rin
F. syriaca (19), F. isaurica (19), F.
pachyloba, F. blancheana, F.
trachycarpa, F. bracteata (78), F.
carduchorum (70), F. trifida (69)
F. capillaris (65)
Marmesin
Dihydrofuranocoumar
in
F. blancheana (78),
(-)-Isovaleryl
Marmesin
Dihydrofuranocoumar
in
F. granatensis (73), F. capillaris (65)
Felamidin (Benzoyl
marmesin)
Dihydrofuranocoumar
in
Prantschimgin (2’’senecioyl
marmesin)
Dihydrofuranocoumar
in
Rutarin
Dihydrofuranocoumar
in
F. pauciradiata (20), F. syriaca (19), F.
isaurica (19), F. pachyloba, F.
trachycarpa, F. bracteata, F.
campestris (79), F. blancheana (78)
F. pauciradiata (20), F. syriaca (19), F.
isaurica (19), F. aucheri (80), F.
bernardii (68), F. pachyloba, F.
trachycarpa, F. bracteata, F.
blancheana (78), F. carduchorum (70),
F. asparagifolia (67), F. trifida (69)
F. asparagifolia(81)
Umbelliprenin
Sesquiterpene
coumarin
F. cassia (8), F. campestris (82-85)
Samarcandin
Sesquiterpene
coumarin
F. campestris (86)
Coladin
Sesquiterpene
coumarin
F. campestris (82, 83)
Coladonin
Sesquiterpene
coumarin
F. campestris (82, 83)
Osthole (Osthol)
Prenylated
coumarin
Osthenol
Prenylated
coumarin
F. brachyloba, F. capillaries (65) F.
campestris (79) F. turcomanica (71), F.
subvelutina (74), F. pachyloba, F.
trachycarpa, F. bracteata, F.
blancheana (78)
F. aucheri (80)
7-Isopentyloxy
coumarin
Prenylated
coumarin
F. campestris (84)
Peucedanol-2’benzoate
Prenylated
coumarin
F. bracteata (78), F. blancheana
Peucedanol
Prenylated
coumarin
F. cassia (8)
Suberosin
Prenylated
coumarin
F. trachycarpa, F. bracteata (78), F.
carduchorum (70), F. trifida (69), F.
trachycarpa (14), F. cassia (8)
Suberosin epoxide
Prenylated
coumarin
F. angulata(87)
Suberenol
Prenylated
coumarin
F. carduchorum (70), F. trifida (69)
Grandivitinol
Prenylated
coumarin
F. pachyloba, F. trachycarpa, F.
bracteata, F. blancheana (78), F.
cassia (8)
Grandivittin
Prenylated
coumarin
F. campestris (79), F. asparagifolia
(67), F. trifida (69)
Ulopterol
Prenylated
coumarin
F. trachycarpa (14, 78), F. trifida (69),
Auraptene
Prenylated
coumarin
F. brachyloba (65), F. campestris(84)
Agasyllin
Pyranocouma
rin
F. campestris (79), F. asparagifolia
(67)
Benzoyl aegelinol
Pyranocouma
rin
Pyranocouma
rin
F. campestris (79)
Aegelinol
F. asparagifolia (67)
Asparagifolin
Pyranocouma
rin
F. asparagifolia (67)
Decursin
Pyranocouma
rin
F. campestris(86)
4’’-hydroxy
Grandivittin
Pyranocouma
rin
F. macrocarpa (88)
Isorhamnetin
Flavonoid
F. sylvatica (89)
Isorhamnetin-3-Ogalactoside
Flavonoid
F. aucheri (80), F. asperigifolia (67)
Rutin
Flavonoid
F. asparagifolia (67)
Hesperetin
Flavonoid
F. carduchorum (70)
6-hydroxy apigenin
6-methyl ether
Flavonoid
F. aucheri (80)
Quercetin
Flavonoid
F. sylvatica (89), F. angulata (90)
Quercetin 3-Oglycoside
Flavonoid
F. confuse (91)
Rhamnetin
Flavonoid
F. asparagifolia(67)
()-angelicoidenol-2O-b-apiofuranosyl(1/6)-bglucopyranoside
Othercompound
F. asparagifolia (67)
Quinol monoacetate
Othercompound
F. aucheri (80)
Dillapiole
Othercompound
F. thyrsiflora, F. nodosa, F. sylvatica
(45)
Lupanine
Othercompound
F. thyrsiflora (45)
3,5-di-(E,E)caffeoylquinic acid
Othercompound
F. asparagifolia (67)
Chlorogenic acid
Othercompound
F. asparagifolia (81)
Polycerasoidin
Othercompound
F. angulata (92)
siol anisate
Othercompound
F. campestris (82, 83)
Ferutinin
Othercompound
F. campestris (82, 83)
Myristicin
Othercompound
F. antiochia (93)
1-acetyl-5-angeloyl
lapiferol
Othercompound
F. campestris (82, 83)
2-epilaserine
Othercompound
F. campestris (82, 83)
Epihelmanticine
Othercompound
F. campestris (82, 83)
9-epoxyfalcarindiol
Othercompound
F. campestris (82, 83)
Nonacosane
β-Sitosterol
Othercompound
Othercompound
F. bernardii (68)
F. pachyloba, F. trachycarpa, F.
bracteata, F. blancheana (78), F.
carduchorum (70)
b-sitosterol
linoleate
Othercompound
F. angulata (77), F. subvelutina (74)
Stigmasterol
Othercompound
F. pachyloba, F. trachycarpa, F.
bracteata, F. blancheana (78), F.
angulata (77), F. macrocarpa(41)
Table 3. Chemical compounds isolated from the Ferulago genus.
Pharmacological activities
In the last two decades, many ferulago species have been widely studied with advanced scientific
methods and reported for several pharmacological properties such as antibacterial activity,
antioxidant activity, antidiabetic activity, larvicidal activity, Alzheimer, and anticancer activity.
These pharmacological activities of Ferulago are considered to be attributed mainly to its
coumarins and furanocoumarins and essential oil (66). Table 4 depicts pharmacological activity
and model of study of the genus Ferulago.
Antibacterial activity
The volatile oils of many herbs of genus Ferulago have been the focus on pharmacological
activity, particularly from an anti-oxidant, antimicrobial and antifungal point of view (7, 20, 29).
In the literature, antimicrobial and antifungal properties of essential oil were screened versus
Gram-positive (Staphylococcus aureus, S. epidermidis, and methicillin-resistant S. aureus), and
Gram-negative (Escherichia coli, Salmonella typhimurium, Bacillus cereus, Proteus vulgaris,
Enterobacter aerogenes, and Pseudomonas aeruginosa) bacteria, and the yeast (Candida
albicans, C. parapsilosis, and C. tropicalis) via broth microdilution assay. Sucu et al., 2019,
studied the antimicrobial effects of volatile oil from the roots and aerial parts of F. sandrasica
and found that both essential oils were not active against C. tropicalis and C. parapsilosis
compared to positive controls (55). The volatile oil of the aerial portions was found to be active
against Salmonella typhimurium, Staphylococcus aureus, and Bacillus subtilis, however, inactive
against E. coli; the root essential oil was active against B. subtilis and S. typhimurium compared
with E. coli, but not active against S. aureus. Recently, Karakaya et al. assessed antimicrobial
activity of n-butanol, ethyl acetate, dichloromethane, methanol extracts, and aqueous residue
parts of methanol extracts from the aerial parts and roots of four Ferulago species (F. pachyloba,
F. bracteata, F. trachycarpa, and F. blancheana) along with 14 isolated compounds via micro
broth-dilution methods. Their result demonstrated that the best antimicrobial effect against B.
subtilis, E. coli, S. aureus, P. aeruginosa, and C. albicans were obtained with methanol extract
of the roots, n-butanol fractions, and methanol extract of the aerial parts from F. blancheana
(62.5 µg/mL), dichloromethane fraction of the roots and aerial parts from F. pachyloba (62.5,
31.25 µg/mL), the n-butanol fraction of the aerial parts, dichloromethane fractions of the aerial
parts and roots, methanol extracts and ethyl acetate fraction of the roots from F. bracteata (62.5
µg/mL), dichloromethane fraction of roots, and methanol extracts of roots and aerial parts from
F. trachycarpa (62.5 µg/mL) and prantschimgin (31.25 µg/mL)(78). According to them, the E.
coli was less affected than the other microorganisms; the best activity against C. albicans (MIC =
31.25 μg/mL) obtained by the CH2Cl2 fraction of aerial portions from F. pachyloba and isolated
compound prantschimgin. Furthermore, Pinto et al. evaluated the antifungal effects of an
essential oil, and two main compounds of it on germ tube formation, ergosterol biosynthesis, and
mitochondrial function. Limonene presented a weaker activity (0.32 to 20μL/mL) than the
essential oil and α-pinene with low and similar to MIC and MFC values against the tested
organisms (0.08 to 5.0μL/mL). The essential oil of F. capillaris suppressed germ tube formation
at sub-inhibitory dose on Candida albicans. The mechanism of antifungal activity of F.
capillaris indicated no distribution on the ergosterol content and defect of mitochondrial role in a
dose-dependent way in essential oil-treated C. albicans (62).
Anti-oxidant effect
In the recent decades, extensive studies have been conducted on the evaluation of the antioxidant
function of medicinal plants as a source of natural compounds not only to combat several
degenerative disorders, including cardiovascular disease and cancer, but also as a substitute
compound to artificial additives, like butylated hydroxytoluene (BHT) and butylated
hydroxyanisole (BHA) in food productions (94). Anti-oxidant constituents diminish the extent of
oxidative damage via acting as free radical scavengers (95). There are numerous methods, such
as radical scavenging power, reducing power, and inhibition of lipid peroxidation in a βcarotene–linoleate system for assessing the antioxidant activity of plant extracts or volatile oils
(96). The DPPH radical-scavenging method is one of the easiest and rapid tests for evaluating the
antioxidant activity of natural compounds(16). According to literature, an antioxidant activity
study has been performed on F.macrocarpa, F. carduchorum (97), F. bernardii (16), F.
sandrasica, F.macedonica, F. trifida (64), F. subvelutina (74), F. cassia (8), F. angulata, and F.
campestris (79). The antioxidant activities of four fractions and crude extract of aerial portions of
F. carduchorum at 2 vegetative periods (flower and fruit) were assessed using the DPPH method.
The best activity belonged to flower crude extract (IC50=0.44 mg/mL)(97). Shahbazi and Shavisi
investigated the antioxidant activities of nonpolar and polar sub-fractions of methanolic extract,
and the volatile oil of the aerial parts of F. bernardii and compared them to BHT via DPPH
assay. The antioxidant activity with the mean of IC50 were polar sub-fractions (5.66), non-polar
sub-fractions (6.88), and essential oil (14.81), while they displayed lower radical scavenging
activity compare with BHT(16). Tavakoli et al. found that due to lack of phenolic compounds in
the conformation of the volatile oil of different parts of F. trifida, a feeble free radical
scavenging effects was observed (IC50: 95–120 μg ml−1) compare to BHT (IC50: 21.2 ± 2.6 μg
ml−1)(64). Moderate antioxidant activities were attained with DPPH test from isolated coumarin
of the roots of F. subvelutina compare to BHT (IC50= 27 µg/mL) > oxypeucedanin hydrate
(IC50= 160 µg/mL) >meranzin hydrate (IC50=180 µg/mL) >osthole(IC50 = 27 µg/mL)
>oxypeucedanin (IC50= 217 µg/mL) >isoimperaturin(IC50= 245 µg/mL) > xanthotoxin (IC50=
270 µg/mL)(74). In another study, the antioxidant activity of isolated compound, and the extracts
and fractions of the aerial parts, fruits, flower, and roots of F. cassia were investigated via TBA
assay. The highest antioxidant potential was obtained based on following order: Peucedanol
(IC50 = 18.1 µg/mL)>Suberosin (IC50 = 23.5 µg/mL)> roots CH2Cl2fractions (IC50 = 43.1
µg/mL)> fruit CH2Cl2 fractions (IC50 = 54.4 µg/mL) > Grandivitinol (IC50 = 61.1 µg/mL) >
Umbelliferone (IC50 = 79.5 µg/mL)(8).
Pharmacological
activities
Anti-microbial
Anti-fungal
Anti-oxidant
Alzheimer
Anti-diabetic
Anti-coagulant
Anti-malaria
Aphrodisiac
Plant
Model
References
F. sandrasica
F. pachyloba, F. blancheana, F.
trachycarpa, F. bracteata
F. capillaris
F. carduchorum
F. bernardii
F. trifida, F. sandrasica, F.macedonica,
F. cassia
F. angulata, and F. campestris
F. subvelutina
F. subvelutina, F. angulata
F.pauciradiata
F. carduchorum
F. isaurica and F. syriaca.
F. trifida
F. angulata
F. pauciradiata
F. blancheana, F. pachyloba, F.
trachycarpa
F. carduchorum
F. carduchorum
F. trifida
F. syriaca
In-vitro
In-vitro
[55]
[78]
In-vitro
In-vitro
In-vitro
In-vitro
In-vitro
In-vitro
In-vitro
In-vitro
In-vitro
In-vitro
In-vitro
In-vitro
In-vitro
In-vitro
In-vitro
[62]
[97]
[16]
[64]
[8]
[79]
[74]
[98]
[20]
[34]
[19]
[64]
[99]
[20]
[100]
In-vivo
In-vitro
In-vitro
In-vitro
[17]
[101]
[102]
[103]
Table 4. Pharmacological activities and model of study of the genus Ferulago.
Alzheimer disease (AD)
Alzheimer is one of the neurological disorders with decreasing acetylcholine followed by the
deterioration of short-term memory, which occurs in elderly people mostly based on genetic
inheritance. One promising strategy for combating AD is using anticholinesterases or
acetylcholinesterase inhibitors (AChEIs) to inhibit the hydrolysis of acetylcholine and raise its
level in the synaptic cleft (82). Hajimehdipoor and co-worker studied the acetylcholinesterase
inhibitory property of the total extracts and fractions of the aerial portions of F. subvelutina and
the whole plant of F. angulata employing the Ellman method. Their result implied that a total
extract of both Ferulago genes have the ability to inhibit the acetylcholinesterase enzyme with
19.7% and 15.8% respectively for F. subvelutina and F. angulata. The dichloromethane fraction
displayed the highest AChEI activity among all the fractions (98). Golfakhrabadi et al. found that
all the coumarins obtained from the aerial parts of F. carduchorum have AchE enzyme
inhibition, among which xanthotoxin revealed the highest inhibitory (IC50=39.64 µM) (70). The
essential oil of F. carduchorum has been also found to be of AChE inhibitory activity (IC50=
23.6 µl ml-1) (34). In another study on AChE inhibitors via a bioassay-guided isolation, the
dichloromethane extract from the root of F. campestris was investigated. Three daucane ester
derivatives (1-acetyl-5-angeloyl lapiferol, ferutinin, and siol anisate), two phenol derivatives
(epielmanticine and 2-epilaserine), one polyacetylene (9-epoxyfalcarindiol), and three coumarin
derivatives (coladin, coladonin, umbelliprenin) were isolated. All the obtained constituents had
the ability to inhibit the AChE, but at higher doses (IC501.2–0.1 mM) than the standard
galantamine (6.7μM) and the most active compounds were the epielmanticine and the siol
anisate with IC50 of 0.172 and 0.175 µM, respectively (82). In addition, Karakaya and co-worker
studied the anticholinesterase effects of the fractions and extracts from the aerial parts and roots
of F. isaurica and F. syriaca. Strong inhibitory activities against butyryl cholinesterase (BuChE)
(88.56 ± 2.34%) and AChE (46.99%) at 20 µg/mL were observed in the CHCl3 part of the root
of F. Isaurica. Felamidin (77.11%); prantschimgin (74.82%), two obtained constituents from
chloroform part of roots, presented a strong inhibitory effect against BuChE (19). In another
study, AChE inhibitory activities of the volatile oils of the fruits, roots, and flowers of F. trifida
were investigated. The result revealed significant AChE inhibitory activity (78.7, 74.3, and 72.1
% inhibition of Ach Enzyme, respectively) (64). Hritcu and co-worker found the volatile oil
extracted from the aerial part of F. angulata has an anti-amnesic activity in scopolamine-induced
memory deterioration in rats and diminish AChE activity in hippocampal (99). In another study
the volatile oil from fruits of F.pauciradiata revealed strong inhibitory properties against
BuChE and AChE (IC50= 0.567, 7.987 l/ml, respectively)(20).
Anti-diabetic effects
α-glucosidase, and α-amylase inhibitory activity of the extracts and some compounds from the
roots of F. blancheana, F. trachycarpa, and F. pachyloba have been evaluated by in-vitro
bioassay-guided isolation methods to determine the anti-diabetic properties of this plant. The
obtained result demonstrated that the highest activities versus α-glucosidase with an IC50 value of
0.3, 2, 2 mg/mL belonged to CH2Cl2 extracts of the roots of F. trachycarpa, F. pachyloba, and
F. blancheana, respectively. Suberosin and felamidin compounds possessed momentous αglucosidase inhibitory activities with IC50 values of 0.9 and 0.4 mg/mL, respectively, while the
IC50 for acarbose as standard was 4.9 mg/mL. The acarbose depicted a strong α-amylase
inhibitory activity (82.3%) at a dose of 1 mg/mL whereas none of the other extracts displayed
significant α-amylase inhibitory effect (100).
Anti-coagulant activity
Golfakhrabadi et al. evaluated the toxicological profile of oral application of the F. carduchorum
extract and the anticoagulant effects of two isolated coumarins (suberenol and suberosin) in male
Wistar rats. The LD50 of the plant extract for acute toxicity was over 2000 mg/kg and there were
no substantial variations (p>0.05) among the control and the treated groups concerning the
biochemical and hematological parameters. The prothrombin time (PT) of the treated group with
total extract from the aerial part of the plant has not shown a major impact relative to the control
group (receiving tap water by gavage) (p>0.05) at doses of 250 and 500 mg/kg. Meanwhile,
suberosin expanded the PT at doses of 3 and 6 mg/kg (16.7 and 17.4 s, respectively) and
suberenol at the same dose (16.5 and 17.1 s, respectively)(17).
Anti-malaria
Khanavi et al. assessed the larvicidal activity of chloroform, methanol, ethyl acetate, and the total
80% methanol extract from the aerial part of F. carduchorum against late 3rd, and early 4th instar
larvae of malaria vector Anopheles stephensi. The LC90 of chloroform, ethyl acetate, the total
extract, and methanol fractions were 0.455, 1.892, 1.509, and 10.886 ppm, respectively.
Moreover, the LC50 of chloroform, ethyl acetate, the total extract, and methanol fractions were
0.236, 0.744, 0.480, and 3.702 ppm, respectively. The chloroform fraction indicated lower LC50
and LC90 values than the other extracts, which might be due to the presence of a high content of
phytosteroids and coumarins (101). In another study, larvicidal activity of a few isolated
coumarin, methanol, and chloroform extracts of the roots, leaves, and fruits of F. trifida were
investigated on the third instar larvae of A. stephensi Listonas. Strong insecticidal properties
were founded for methanol extract of the fruit with LC90 and LC50 values of 18.12 and 2.94 ppm,
respectively. Among pure compounds, oxypeucedanin presented moderate toxicity against A.
stephensi with LC90 and LC50 values of 346.41 and 116.54 ppm, respectively. It could be
concluded that the methanol extract from the fruit of F. trifida might be utilized as an effective
bio-insecticide in green control programs of mosquitoes, particularly A. stephensi (102).
Aphrodisiac activity
An in-vitro study was conducted by Ozturk et al. to investigate the aphrodisiac activity of the
lyophilized water extract from the roots of F. syriaca on human corpus cavernosum. For finding
the mechanism involving in relaxation, the effect of the extract was investigated on the relaxing
responses to selective guanilate cyclase inhibitor (oxadiazolo [4,3-α] quinoxalin-1one (ODQ)),
NO-synthesis inhibitor (NG-nitro-L-arginine methyl ester (L-NAME)), forskolin, Electrical field
stimulation (EFS), sodium nitroprusside, and acetylcholine. The result displayed that the extract
could have to relax in a dose-dependent way on corpus cavernosum strips, and the L-NAME
(small dosages) and QDQ (in all dosage) were able to suppress the extract-induced relaxation in
the human corpus cavernosum. The F. syriaca extract enhanced the relaxation response of strips
with Ach incubation while the extract did not affect the relaxation induced by EFS, forskolin
sodium, and nitroprusside. The result suggested that the extract of F. syriaca could possibly act
via stimulating the NO- cyclic guanosine monophosphate (cGMP) pathway (103).
Toxicity profile of the genus Ferulago
Nowadays, the usage of herbal remedies has increased around the world, and patients falsely feel
that they are healthy because they are natural. While these products comprise several bioactive
compounds and might cause adverse effects on consumers (104, 105). Therefore, it is essential to
herbal medicines undergo current safety and efficacy tests. Based on the literature review, there
is only one piece of scientific study about the safety of this herb. Golfakhrabadi et al.
investigated oral acute, and sub chronic toxicities of the total extract of the aerial parts of F.
carduchorum in the rat (17). To study acute toxicity five rats were treated with one dose of the
total extract (2000 mg/kg) orally and the control group was treated with tap water. For the sub
chronic study, the doses (250, 500, and 1000 mg/kg) of the total extract applied to treated groups
by gavage for thirty following days. During the acute toxicity study, the animals did not show
any signs of side effects, mortality, and the LD50 was over 2000 mg/kg in rats. The result of sub
chronic toxicity demonstrated that the total extract did not yield momentous changes in behavior,
water and food intake, breathing, body weight gain, blood metrics, and gastrointestinal properties
in rats (17). This study indicated that F. carduchorum may be a healthy additive for conventional
applications.
Conclusion and future perspective
To date, around 73 molecules, including coumarin, furanocoumarin, flavonoids, and stilbene
have been isolated from the Ferulago species. Among the isolated constituents, mostly are
phenolic compounds in which three simple coumarins, sixteen furanocoumarins, five dihydrofuranocoumarin, four sesquiterpene coumarin, twelve prenylated coumarins, six
pyranocoumarin, nine flavonoids, and eighteen miscellaneous compounds. Coumarins and their
derivatives are considered to be important taxonomic markers of the genus Ferulago. In the
pharmacological effect part, we have discussed various studies to evaluate the ethnomedicinal
uses and this has shown that the isolated constituents and different extracts from the Ferulago
species possess several pharmacological effects including antibacterial, antioxidant, Alzheimer,
anti-diabetics, anti-malaria, anti-cougulant, aphrodisiac effects. Accessible information regarding
Ferulago spp. allows us to explore their potential benefits, highlight the gaps in our knowledge,
and conduct future researches order to develop new drugs. It can be concluded that the
pharmacological study of Ferulago spp. are in agreement with the ethnomedicinal uses of the
plants.
Acknowledgements
This work was a part of PhD project and financially supported by Tabriz University of Medical
Sciences, Tabriz, Iran [Grant Number: 64064].
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Yahya Rahimpour